The nuclear deubiquitinase BAP1 is commonly inactivated by somatic mutations and 3p21.1 losses in malignant pleural mesothelioma

Matthew Bott, Marie Brevet, Barry S. Taylor, Shigeki Shimizu, Tatsuo Ito, Lu Wang, Jenette Creaney, Richard A. Lake, Maureen F. Zakowski, Boris Reva, Chris Sander, Robert Delsite, Simon Powell, Qin Zhou, Ronglai Shen, Adam Olshen, Valerie Rusch, Marc Ladanyi

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401 Citations (Scopus)

Abstract

Malignant pleural mesotheliomas (MPMs) often show CDKN2A and NF2 inactivation, but other highly recurrent mutations have not been described. To identify additional driver genes, we used an integrated genomic analysis of 53 MPM tumor samples to guide a focused sequencing effort that uncovered somatic inactivating mutations in BAP1 in 23% of MPMs. The BAP1 nuclear deubiquitinase is known to target histones (together with ASXL1 as a Polycomb repressor subunit) and the HCF1 transcriptional co-factor, and we show that BAP1 knockdown in MPM cell lines affects E2F and Polycomb target genes. These findings implicate transcriptional deregulation in the pathogenesis of MPM.

Original languageEnglish
Pages (from-to)668-672
Number of pages5
JournalNature Genetics
Volume43
Issue number7
DOIs
Publication statusPublished - Jul 1 2011

ASJC Scopus subject areas

  • Genetics

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    Bott, M., Brevet, M., Taylor, B. S., Shimizu, S., Ito, T., Wang, L., Creaney, J., Lake, R. A., Zakowski, M. F., Reva, B., Sander, C., Delsite, R., Powell, S., Zhou, Q., Shen, R., Olshen, A., Rusch, V., & Ladanyi, M. (2011). The nuclear deubiquitinase BAP1 is commonly inactivated by somatic mutations and 3p21.1 losses in malignant pleural mesothelioma. Nature Genetics, 43(7), 668-672. https://doi.org/10.1038/ng.855